Bioorganic & medicinal chemistry
July 15, 2015
Martin Hansen, Stine Engesgaard Jacobsen, Shane Plunkett et al.
35 citations
N-Benzyl substitution dramatically alters how phenethylamine 5-HT2A receptor agonists bind to and activate serotonin receptors. This work examined how adding an N-benzyl group to 4-bromo-2,5-dimethoxyphenethylamine derivatives affects affinity for 5-HT2A and 5-HT2C receptors, focusing on the 2' and 3' positions of the benzyl ring. Substitutions at these positions were generally well tolerated. Probing the 2' position with various substituents revealed that small changes profoundly affected affinity, and two ligands lacking a 2'-benzyl substituent unexpectedly showed high affinity, contradicting earlier assumptions. Several high-affinity ligands were tested for functional activity and were less efficacious agonists than previously reported N-benzyl phenethylamines.
Bioorganic & medicinal chemistry
May 1, 2012
Kimberly M Lovell, Tamara Vasiljevik, Juan J Araya et al.
35 citations
A palladium-catalyzed cross-coupling reaction (Liebeskind-Srogl) applied to a modified natural product scaffold produces ketone analogs of salvinorin A at neutral pH and room temperature, expanding synthetic access to this class. A one-step microwave method converts salvinorin A to its 12-epimer, previously requiring multiple steps. Several new analogs (alkene 9 and aromatic compounds 12, 19, 23, 25, 26) retain affinity and selectivity for kappa opioid receptors (KOP), and the furan-2-yl analog (31) shows similar affinity to the parent compound. These results indicate that diverse aromatic groups attached to the decalin core may be tolerated by KOP receptors, potentially yielding additional ligands.
Bioorganic & medicinal chemistry
March 20, 2003
Daniele Passarella, Raffaele Favia, Alessandra Giardini et al.
23 citations
A method to synthesize 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes using cycloaddition followed by cross-coupling is described. The binding affinity of these new compounds to the receptor targets characteristic of ibogaine is reported.
Bioorganic & medicinal chemistry
January 17, 2026
Uriel Matthew Enriquez, Natalie M González Velázquez, Mohammad Mosharraf Hossain et al.
Monoclonal antibodies were developed that specifically recognize (2R,6R)-hydroxynorketamine, a metabolite of ketamine linked to rapid antidepressant effects. An immunogenic bioconjugate was designed by attaching a 6-aminohexanoic acid linker to the pharmacophore and coupling it to a carrier protein. Mice immunized with this conjugate produced equivalent antibody titers to a racemic comparator. Hybridoma screening yielded the monoclonal antibody 6F11-HC1-LC2, which showed strong binding to (2R,6R)-hydroxynorketamine but no response to the (2S,6S) enantiomer in competitive ELISA. Surface plasmon resonance revealed sub-nanomolar affinity (0.4 nM) for (2R,6R)-hydroxynorketamine-BSA conjugates and over 150-fold selectivity over ketamine-BSA conjugates. These antibodies can be used in future studies to investigate the roles of hydroxynorketamine enantiomers in ketamine's antidepressant effects.